Deep Brain Stimulation surgery experience at Apollo Hospital, New Delhi

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Functional neurosurgery is concerned with the treatment of conditions where central nervous system (brain and spinal cord) function is abnormal although the structure or anatomy is normal. Eighty-seven Deep Brain Stimulation surgeries were done at Indraprastha Apollo Hospital, New Delhi since year 2000. This included 81 cases of Parkinson’s disease (STN stimulation), 4 cases of Essential Tremors (VIM thalamic nucleus stimulation) and three cases of Dystonia (Globus Pallidus stimulation). All the patients showed good response and one patient developed small thalamic hemorrhage which improved over a period of six weeks.





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Deep Brain Stimulation surgery experience at Apollo Hospital, New Delhi

  1. 1. Deep Brain Stimulation surgery experience at Apollo Hospital, New Delhi
  2. 2. a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 1 8 8 e1 9 2 Available online at www.sciencedirect.com journal homepage: www.elsevier.com/locate/apme Research Article Deep Brain Stimulation surgery experience at Apollo Hospital, New Delhi Sudheer Tyagi Sr. Consultant Neurosurgeon, Indraprastha Apollo Hospital, New Delhi, India article info abstract Article history: Eighty-seven Deep Brain Stimulation surgeries were done at Indraprastha Apollo Hospital, Received 23 July 2013 New Delhi since year 2000. This included 81 cases of Parkinson’s disease (STN stimulation), Accepted 8 August 2013 4 cases of Essential Tremors (VIM thalamic nucleus stimulation) and three cases of Dystonia (Globus Pallidus stimulation). All the patients showed good response and one patient developed small thalamic hemorrhage which improved over a period of six weeks. Keywords: Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved. Parkinson’s disease Dystonia Essential Tremors 1. Introduction Functional neurosurgery is concerned with the treatment of conditions where central nervous system (brain and spinal cord) function is abnormal although the structure or anatomy is normal. Horsley and Clarke1 were the first to put stereotactic principles into practice: they designed a stereotactic frame for laboratory experiments that directed a probe to a predetermined target located in the brain within a three dimensional reference grid. The lateral was based on the location of the midsagittal plane, the external auditory meatus and the orbital meatus plane. The principles could not unfortunately be applied to the human brain because of the variability of the skull dimensions. The breakthrough in the development of human stereotactic surgery came in 1947 when Spiegel and Wycis2 used landmarks within the brain, rather than the skull. Locating brain targets with reference to the ventricular system, outlined by contrast medium. Sweet and Mark3 introduced the use of radio frequency current in 1960, and this was a major factor in bringing stereotactic functional neurosurgery to its present sophistication. Further development of functional neurosurgery occurred hand-in-hand with the development of computer techniques for complicated calculations and display online graphics of the mass of data collected during surgery. The development of imaging techniques gave another boost in 3-dimensional radiological localization of ventricular landmarks and different brain targets with reference to a suitable brain atlas. Image fusion technique was used at Apollo Hospital, New Delhi, to utilize CT scans as well as MRI data to use collectively for target localization in cases of Deep Brain Stimulation surgery. E-mail address: sudheerktyagi@gmail.com. 0976-0016/$ e see front matter Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved. http://dx.doi.org/10.1016/j.apme.2013.08.012
  3. 3. a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 1 8 8 e1 9 2 2. Indications of Deep Brain Stimulation surgery The Functional Stereotactic Neurosurgery was first used by Spiegel et al4 in a case of Huntington’s Chorea. They made a pallidal lesion in this case followed by many cases of Parkinsonism. After successful outcome of Functional Stereotactic Neurosurgery in movement disorders it was followed by its use in psychiatric illnesses, intractable pain, epilepsy and cerebral palsy. With the advent of Levodopa in 1968 interest in stereotactic surgery for Parkinson disease waned but over the next 15 years an increasing number of Parkinson’s patients with dopa dyskinesias and motor fluctuations led to a resurgence in Functional Stereotactic surgery. Adrenal medullary grafts and transplantation of fetal dopamine cells into the striatum has remained mostly an experimental procedure. In the late 1980s pallidotomy was revisited and by the mid 1990s many groups had confirmed its efficacy, particularly for alleviating levodopa-induced dyskinesias. Expertise and confidence in these techniques were rekindled but concern remained regarding high complication rates, particularly when bilateral lesions were required.5,6,7 Next revolution came with the invention of Deep Brain Stimulation Technique. Initially two patients of multiple sclerosis induced tremors were treated by fully implantable thalamic stimulators. Experience increased and technology improved. In 1993 Benebid reported stimulation of the subthalamic nucleus (STN), which improved almost all parkinsonian symptoms allowing substantial reduction of dopaminergic medication.8 3. DBS in Parkinson’s disease 3.1. Patient selection Surgical intervention is usually reserved for patients with advanced Parkinson’s disease when medical treatment has been exhausted. Apart from tremor response, the outcome of surgery for Parkinson’s disease is dependent upon the presence of dopaminergic responsive symptoms to be effective but at the same time non-dopa responsive Parkinson diseases, such as multiple system atrophy, will not significantly benefit from surgery. The criteria of patients for surgery are listed. It is important that patients with significant cognitive or psychiatric difficulties are not considered for surgery. Patients with drug-induced hallucinosis, postural instability and dysphonia are usually not good candidates. The temptation to offer surgery because nothing more can be done, has often lead to disaster. Some patients prefer to surgery without a trial of medication, despite a thorough counseling. Early surgery may be appropriate for tremor predominant disease (particularly “benign tremulous” Parkinson’s disease), but for other types, the balance between side effects and efficacy is not adequate to recommend surgery early in the course of the disease.6 3.2. 189 Surgical technique The outcome of functional stereotactic surgery is dependent upon the precise localization of correct target that is why different imaging techniques are used to locate the target and with neurophysiological reconfirmation intraoperatively is usually fitted under local anesthesia and patient remains conscious throughout the surgical procedure to allow clinical confirmation of symptom effectiveness and side effects. Patients without significant tremor or rigidity in the “off” state are difficult to assess intraoperatively. Bradykinesia seldom responds to stimulation and therefore cannot be reliably used. Microelectrode recording has been used to map out the various nuclei neurophysiologically.9 This can add to the length of the surgical procedure, which in some centers with the bestpublished outcomes often take more than 12 h! On stimulation or lesioning of the pallidum or STN, transient dyskinesias may occur, which usually indicate successful outcome. All in all the procedure is remarkably well tolerated. 3.3. Intraoperative neuro stimulation Stimulation is probably still the most widely used method of physiological localization.10 However, the problem of current spread must be kept in mind. Only threshold responses are meaningful; suprathreshold responses result in indiscriminate current spread. Stimulation mapping is most productive if performed methodically at intervals of say, 2e3 mm. Interpretation is facilitated if trajectories are arranged in a single sagittal plane by placing the access burr hole in the same sagittal plane as the intended target. Electrode with 1.9 Â 4.0 mm uninsulated tip is preferred and frequency of 2 Hze130 Hz is used for stimulation in 2 mm steps starting 6 mm above the target. 3.4. Micro electro recording The use of microelectrodes in stereotactic surgery allows assessment of both the spontaneous and evoked activity of neurons. One may recognize a desired target outright by virtue of a distinctive spontaneous firing pattern such as that of the “tremor cells” in the thalamic target for ablative lesions in Parkinson’s disease, or else evoked activity may be distinctive, as in nociceptive neurons in the medial thalamus. On the other hand, as Guiot observed, a target may be located by the identification of structures immediately adjacent, such as, during a procedure for relief ;of dyskinesia, somatosensory neurons that lie immediately caudal to the target.11 Microelectrodes may also be used to serially record spontaneous activity as an electrode is advanced through the brain; this activity is distinctive and can be used to identify each nuclear structure through which the electrode passes.
  4. 4. 190 a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 1 8 8 e1 9 2 Microelectrode recording showing tracings of neuronal discharge from subthalamic nucleus. 3.5. Implantation of microelectrodes for deep brain stimulation Parasagittal burr holes of 15 mm diameter are made, 2 cm lateral to midline just anterior to coronal suture. A plastic ring of corresponding size is fixed over the burr holes. The dura is incised in a way that CSF should not leak and a small cortical incision is made. At a time only one microelectrode implantation can be carried out, the microelectrode is guided into the brain through the burr hole according to XYZ coordinates fixed on the frame. Microelectrode implantation for deep brain stimulation is best done with the help of micro guide along with microelectrode recording (MER). Microelectrode recording helps in precise localization of the tip of microelectrode especially in case of a small target like the subthalamic nucleus. The tip of each electrode has four microelectrodes of which at least three should remain within the nucleus. Neuro stimulation procedure should be carried out at this stage to see for change in rigidity and tremors, which further confirms the correct target localization. After the microelectrode is implanted it should be fixed at the burr hole site with the help of a plastic cap which fits into the already fixed plastic ring in the burr hole. In the same way the opposite side microelectrode implantation is carried out and confirmed by viewing with an image intensifier (C arm).
  5. 5. a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 1 8 8 e1 9 2 3.6. Lesions or stimulation After successful implantation microelectrodes are connected to the neurological pacemaker through the leads, which are passed through a subcutaneous tunnel from burr hole site to the infraclavicular portion of chest where neurological pacemaker is placed through a transverse incision. High frequency electrical DBS provides an adjustable inhibitory effect on the target site, but at increased cost. An accurately placed lesion in the thalamus or pallidum provides reliable long lasting suppression of tremor and dyskinesias respectively, with no adverse effects. Bilateral RF lesions are invariably associated with adverse cognitive and bulbar effects, even when well placed, and stimulation is consequently preferable. Lesioning of the STN is technically demanding because of its small size, and benefits appear to be temporary and therefore stimulation of this target is now recommended. Though effective, DBS requires careful postoperative adjustment that often takes many hours, and the replacement of equipment when hardware failure occurs. In some series up to 20% of wires move, break, or become infected. The stimulation battery unit requires replacement every five years for STN stimulation, and three years for pallidal stimulation. 3.7. Post operative programming Programming is a very important part in cases of deep brain stimulation and good programming makes considerable difference in the post op results. Programming for rigidity, tremor, akinesia and freezing should be done in the off stage and for dyskinesias in the on stage. Channel one in programmer indicates the microelectrode which is implanted in the left side of brain which controls right half of body. Similarly channel two is for microelectrode implanted in the right side of brain which controls the left half of body. Usually the amplitude for STN is kept between 1.5 and 4.0 V and pulse with 60e90 ms. Frequency of current used for STN is usually from 130 to 180 Hz. Electrode configuration can be either Bipolar or Unipolar. In Bipolar setting one electrode is positive and another one is negative and this leads to stimulation of focal region between two electrodes. In Unipolar setting one of the electrode is negative and case of pulse generator is positive and this leads to stimulation of greater area. Repeated programming is required to ensure optimal results. 4. Different targets used in movement disorders according to predominant symptom 4.1. Thalamus The thalamus is the final common outflow pathway for all tremors. Contralateral tremor is reliably suppressed with a lesion in the VIM nucleus and rigidity in the ventralis oralis posterior (Vop) nucleus. There is no effect on bradykinesia and although dyskinesia is occasionally helped, this is certainly not a reliable observation. Even patients with tremor predominant Parkinson’s disease will eventually develop bradykinesia in time, so it is now recommended that such patients should have STN stimulation, rather than a thalamic lesion or stimulation.12 4.2. 191 Globus Pallidus Posteroventral pallidal lesion7 or stimulation will reliably abolish contralateral dyskinesias. This includes biphasic and peak dose, and “off” state dystonias. Following optimal lesioning, the benefit can persist for at least five years. The improvement in “off” state bradykinesia also persists, but any improvement in “on” state dissipates after six months. Contralateral tremor may also be improved but this is not a reliable effect. Globus Pallidus stimulation was done in three selected cases of dystonia at Apollo Hospital, New Delhi. Coordinates for Globus Pallidus internus are 2e3 mm anterior to mid commissural point, 6 mm inferior to ACePC line and 18e22 mm lateral to midline. 4.3. Subthalamic nucleus (STN) Bilateral subthalamic stimulation alleviates all the cardinal symptoms of Parkinson’s disease and benefits are preserved for as long as five years. Unlike pallidal surgery, medication can be reduced by at least half postoperatively, and this leads to a reduction in drug-induced dyskinesias.12,13 Unilateral surgery can be offered to patients with very asymmetric disease, but most require bilateral surgery to avoid problems with variable medication requirements on the two sides. Complications can be transient or permanent and tolerance may develop in some patients. Dramatic rebound symptoms can be seen following acute stimulator failure, sometimes necessitating emergency admission. The current stimulator units are less sensitive to electromagnetic interference, such as from light switches and electric motors. Patients are now usually given control devices that can be preset to alter the stimulation parameters at home. Although the results in well-selected patients can be dramatic and well maintained, SIN stimulation requires considerable long-term commitment from the team looking after the patient. It has been estimated that each patient requires on average 40 h of adjustment for optimum benefit and maintenance of effect. For this reason, it is difficult to envisage this procedure becoming widely available, unless there is a substantial increase in the number of experienced staff in the units offering this service. There is also concern about the frequency of psychiatric side effects, particularly depression that probably arises as a result of the inhibition of STN limbic areas. The rate of suicide has been high in some series, which is rarely seen with surgery to other targets. Patients with a history of significant depression should not be offered STN surgery. Coordinates for subthalamic nucleus are 2e7 mm inferior to mid point of ACePC line and 12.5 mm lateral to midline. STN stimulation was done in 81 cases of Parkinson’s disease. 5. DBS in essential tremor A thalamic VIM lesion will reliably suppress contralateral tremor. Given the bilateral nature of the condition, bilateral thalamic stimulation is now the preferred option. Side effects are similar to those seen in ‘pallidal surgery’ wide. Four cases of essential tremor underwent Deep Brain Stimulation surgery and showed excellent response.
  6. 6. 192 6. a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 1 8 8 e1 9 2 Summary There is no doubt that functional neurosurgery can produce dramatic benefits, with a relatively small risk of adverse effects in experienced hands. The last decade has witnessed the rebirth of neurosurgery for movement disorders with the introduction of Deep Brain Stimulation surgery at different targets in the brain. Improvement in stimulator design should eliminate the need for battery changes and may also permit simultaneous stimulation at multiple targets further broadening surgical option. Advances in frameless stereotaxy may soon allow DBS implantation without the need for a stereotactic frame. The long-term future, however, lies in therapies aimed at altering the course of disease by possibly neural grafting and in vivo gene therapy. Conflicts of interest The author has none to declare. references 1. Horsley V, Clarke RH. The structure and functions of the cerebellum examined by a new method. Brain. 1908;31:45e125. 2. Speigel EA, Wycis HT, Baird III HW. Pallidotomy and pallidoamygdalotomy in certain types of convulsive disorders. Arch Neurol Psychiatry. 1958;80:714e728. 3. Spiegel EA, Wycis HT. Pallidotomy in chorea. Arch Neurol Psychiatry. 1950;64:295e296. 4. Spiegel EA, Wycis HT, Marks M, Lee AJ. Stereotaxic apparatus for operations on the human brain. Science. 1947;106:349e350. 5. Gabriel EM, Nashold BS. Evaluation of neuroablative surgery for involuntary movement disorders: an historical review. Neurosurgery. 1999;42:575e591. 6. Gildenberg PL. Current indications for stereotactic surgery in Parkinson’s disease. Med J St Jos Hosp (Houston). 1981;16:219e223. 7. Knight G. Stereotactic tractotomy in the surgical treatment of mental illness. J Neurol Neurosurg Psychiatry. 1965;28:304e310. 8. Benabid AL, Benazzouz A, Hoffman D, Limousin P, Krack P, Pollak P. Long-term electrical inhabitation of deep brain targets in movement disorders. Mov Disord. 1998;13(suppl 3):S119eS125. 9. Guiot G, Derome P, Arfel G, Walker S. Electrophysiological recordings in stereotaxic thalamotomy for parkinsonism. Prog Neurol Surg. 1973;5:189e211. 10. Hassler R, Richert T. Uber die Fall von doppelseitiger Fornicotomie bei sogenannter temporaler Epilepsie. Acta Neurochir (Wien). 1957;5:330e340. 11. Gross RE, Lozano AM. Advances in neurostimulation for movement disorders. Neurol Res. 2000;22:247e258. 12. Leksell L, Jenberg B. Stereotaxis and tomography: a technical note. Acta Neurochir (Wien). 1980;52:1e7. 13. Benabid AL, Pollak P, Gervason C, et al. Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus. Lancet. 1991;337:403e406.
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